Is KIF1B p.Asp1326Val (c.3977A>T) pathogenic?

KIF1B p.Asp1326Val (c.3977A>T) is classified Uncertain significance in KIF1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-19). AlphaMissense: ambiguous (0.4253); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with KIF1B p.Asp1326Val (c.3977A>T)?

KIF1B p.Asp1326Val (c.3977A>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is KIF1B p.Asp1326Val (c.3977A>T) in the general population?

KIF1B p.Asp1326Val (c.3977A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIF1B p.Asp1326Val (c.3977A>T)?

AlphaMissense predicts ambiguous (score 0.4253) — an in-silico prediction, not a clinical call.

KIF1B p.Asp1326Val

c.3977A>T · rs879368394 · VCV1433407

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4253 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.4253	ambiguous
REVEL	0.702	pathogenic-leaning
SaProt	LLR -8.58	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 69 kb · p 1.9e-20 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KIF1B
Protein: p.Asp1326Val
Coding: c.3977A>T
MANE Select: NM_001365951
dbSNP: rs879368394
Type: single nucleotide variant
Location: chr1:10352658 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.64 · 1 PDB

Full KIF1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KIF1B p.Asp1326Asn Uncertain significance ★ ⚠ same residue
KIF1B c.1590+5G>A Uncertain significance ★★ same condition
KIF1B c.1671-3C>A Uncertain significance ★★ same condition
KIF1B c.1671-3C>G Uncertain significance ★★ same condition
KIF1B c.1861+3G>A Uncertain significance ★★ same condition
KIF1B c.2115+6A>T Uncertain significance ★★ same condition
KIF1B c.2358+1G>A Uncertain significance ★★ same condition
KIF1B c.2676-3T>C Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/kif1b-p-asp1326val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown